This invention relates to DNA assay technology. More particularly, it relates to a new and unique, digitally-addressable, pixelated, thin-film-based, DNA fluid-assay micro-structure, and to associated methodologies for making and thereafter using such micro-structure.
DNA sensor, or assay, technology, in general terms, offers great promise for a host of scientifically, medically, and other diagnostically important studies and detection practices. However, this technology is shadowed by a number of important drawbacks to which the present invention directs focused, remedial attention.
Current DNA micro-assay structures typically take the form of substrate-supported fields, or arrays, of synthesized oligonucleotide probes. These probes, when formed, and when readied for use with appropriate, selected sensitivities to predetermined oligonucleotide compounds, are exposed to applied fluid material of DNA interest, and are thereafter prompted to fluoresce under the influence of an illuminating external laser, thereby to produce a “viewable”, image-capturable fluorescence pattern from which an assay interpretation is made utilizing various special templates which are required in order for one to obtain an appropriate image analysis. This imaging and template-based image-analyzing is quite time-consuming, expensive, and prone to inaccuracy.
For many reasons which are well known to those generally skilled in the relevant art, conventional micro-assay DNA probe structures are typically single-use in nature, are complex and very costly to manufacture, and are, on balance, and as was just suggested above, ultimately quite expensive to use. These today-conventional, chip-like micro-array structures, additionally, are often frustratingly inaccurate in performance because of many false-positive responses produced during assays. Further, assays performed with these current structures can be very slow to yield assay results, often taking many hours, and often “overnight”, to do this. Consequently, they do not lend themselves to rapid, high-throughput performance.
In addition to these several, above-mentioned prior-art drawbacks and disappointments, the assortment of equipment required for DNA assay-structure manufacturing and ultimate use is large, and the relevant, required equipment is usually bulky and expensive. In this setting, convenient and desired portability for conventional DNA assay practice in a non-centralized fashion is just not practical or economically possible.
The present invention dramatically addresses these prior-art drawbacks and constraints.
Featured by the invention are a unique, digitally-addressable, pixelated, thin-film-based, DNA fluid-assay, active-matrix micro-structure, and the related making and using methodologies, wherein, using very conventional, basic wafer-scale nano-processing and thin-film techniques, mentioned somewhat more fully below, and which techniques are well known to those skilled in the art, an array of individually digitally addressable, specialized micro-pixels, or pixels, is developed on a supporting substrate, preferably made of glass or plastic, as will be explained more fully below.
Preferably further, and in the above context, the invention takes the form of a relatively inexpensive, consumer-level-affordable DNA assay structure which features a low-cost substrate that will readily accommodate low-cost, and preferably “low-temperature-condition”, fabrication thereon of substrate-supported DNA matrix-pixel “components”. “Low temperature” is defined herein as a being a characteristic of processing that can be done on substrate material having a transition temperature (Tg) which is less than about 850° C., i.e., less than a temperature which, if maintained during sustained material processing, would cause the subject material to lose dimensional stability.
Accordingly, while the DNA matrix-pixel technology of this invention, if so desired, can be implemented on more costly supporting silicon substrates, the preferred supporting substrate material is one made of lower-expense glass or plastic materials. The terms “glass” and “plastic” employed herein to describe a preferred substrate material should be understood to be referring also to other suitable “low-temperature materials. Such substrate materials, while importantly contributing on one level to relatively low, overall, end-product cost, also allow specially for the compatible employment, with respect to the fabrication of supported pixel structure, of low-temperature processes and methods that are based on amorphous, micro-crystal and polysilicon thin-film-transistor (TFT) technology. In particular, these substrate materials uniquely accommodate the use of the just-mentioned low-temperature TFT technology in such a way that electrical, mechanical and electromagnetic field-creating devices—devices that are included variously in the DNA assay micro-structure of the invention—can be fabricated in a “thin-film manner” simultaneously in a process flow which is consistent with the temperature tolerance of such substrate materials.
Regarding the preference herein for the use of low-temperature TFT technology, and briefly describing aspects of that technology, low-temperature TFT devices are formed through deposition processes that deposit silicon-based (or other-material-based, as mentioned below herein, and as referred to at certain points within this text with the expression “etc.”) thin-film semiconductor material (which, for certain applications, may, of course, later be laser crystallized to establish certain desired characteristics). This is quite different from classic silicon CMOS device technology that utilizes a single-crystal silicon-wafer bulk material as its semiconductor material. While the resulting TFT devices may not have the switching speeds and drive capabilities of transistors formed on single-crystal substrates, TFT transistors (electronic switching devices) can be fabricated cheaply with a relatively few number of process steps. Further, thin-film deposition processes permit low-temperature TFT devices to be formed on alternate substrate materials, such as transparent glass substrates, for use, as an example, in liquid crystal displays. In this context, and speaking specifically and illustratively at this point about silicon, it will be understood that low-temperature TFT device fabrication may variously involve the use typically of amorphous Si (a-Si), of micro-crystalline Si, and or of polycrystalline Si formed by low-temperature internal crystalline-structure processing of amorphous Si. Such processing is described in U.S. Pat. No. 7,125,451 B2, the contents of which patent are hereby incorporated herein by reference.
For the sake simply of convenience of expression regarding the present invention, and in order to emphasize the “low-temperature”, thin-film-based formation possibility which is associated with the invention in its preferred form, all aspects of assay-matrix pixel fabrication and resulting structure are referred to herein in the context and language of “low-temperature silicon, etc. on glass or plastic” construction, and also in the context and language of “low-temperature TFT and Si technology”.
Returning attention now to earlier discussion herein, the term “active-matrix” refers to a pixelated structure in which each pixel is controlled by some form of a switching device. Each of these pixels, in what can be thought of as its precursor condition, and with reference to a preferred embodiment of the invention, includes a site readied for hosting at least one, selected, still-to-be-built, DNA oligonucleotide probe, and at least one, adjacent, digitally addressable, pixel-specific, preferably thin-film structure referred to herein as an energy-field-producing functionalizer (and also as an electromagnetic field-creating structure), preferably taking the form of a light source (an optical source) operable at a predetermined wavelength and power level. Such a functionalizer performs as an optical-power energizer/illuminator/field-creator during, and even after, the process of functionalizing a pixel beyond its precursor condition. In particular, such a functionalizer in each pixel is selectively activatible both (a) to play an important energizing role in the post-precursor building (pixel-functionalizing) of a pixel-site-specific oligonucleotide probe, and (b) additionally later, and preferably, to play a key, supplementary role in illuminating the site of that probe with an electromagnetic light field to cause DNA material which has attached to it during a DNA assay to fluoresce during the carrying out of a DNA fluid-assay.
Also included within the site of each pixel (i.e., pixel integrated), in the pixel's precursor condition, is at least one fully pixel-integrated, individually digitally-addressable, pixel-specific optical detector which is employed during a DNA assay to “read” any fluorescence response (created by DNA assay material which has attached to the associated oligonucleotide probe) when that attached-to probe is illuminated by an associated functionalizer.
In the fully-functionalized (i.e., non-precursor) condition of each pixel, there is at least one fully formed, selected, oligonucleotide probe which has been built (i.e., functionalized) with the aid of the mentioned, appropriate, digitally-addressable, pixel-specific functionalizer.
As will become apparent, the “pixel-on-board natures” of the digitally-addressable, pixel-specific functionalizers and optical detectors (a) uniquely address the several above-mentioned issues associated with the prior art, and (b) sharply distinguish this invention from that art.
These and other features and advantages which are offered by the present invention will become more fully recognized as the detailed description thereof which follows below is read in conjunction with the associated drawings.